Iron (Fe) is a trace element that plays an important role as an essential component compositing hemoglobin, myoglobin, cytochrome, iron-sulfur protein, lactoferrin and various enzymes in human body. A normal adult male has approximately 4-5 g of iron in his body and 60% of it exists as a cofactor of hemoglobin in circulating red blood cells while 11% of it exists as iron enzymes that play an important role in metabolism. Another 15-25% is stored in the form of ferritin or hemosiderin.
Iron is not endogenously synthesized but is taken from food. Iron in food is classified into two forms, which are heme-iron and non heme-iron. In animal foods, 40% of the total iron content is heme-iron and the rest 60% of it is non heme-iron. In the meantime, iron included in vegetable foods is all non heme-iron. None of heme-iron has been reported as originated from microorganisms until today. The absorption efficiency of food iron varies greatly according to its form, either heme-iron or non heme-iron. For instance, the absorption rate of iron taken from animal foods is at least 10% and the absorption rate of iron from vegetable foods is 5% at best. In particular, the absorption of non heme-iron is affected by the degree of in vivo iron storage and other dietary factor such as the amount of ascorbic acid. Generally, a healthy adult absorbs only 5-10% of iron taken from foods. Therefore, iron deficiency is a very common nutritional issue over the world. To prevent or treat iron deficiency, iron compounds such as ferric chloride, ferric citrate, ferrous lactate and heme-iron are used as an iron supplements.
The advantage of such inorganic irons, the iron compounds, except heme-iron is that they have high iron content and are inexpensive. However, they demonstrate low in vivo absorption rate and might cause iron poisoning when over-taken. Therefore, heme-iron, the organic iron that shows high absorption rate with less side effects, is in increasing demand.
Heme-iron is largely included in hemoglobin and myoglobin, which is isolated from blood of slaughtered animal. There is a safety issue in using such heme-iron because of the risk of diseased animal, for example there is a chance that the slaughtered animal might have a disease such as bovine spongiform encephalopathy. Besides, iron content in hemoglobin is very low, so that over-taking is demanded, resulting in excessive taking of protein. Thus, it is still requested to develop a heme-iron preparation that is safe and efficient.
Heme-iron is a porphyrin complex containing iron atom. The biosynthesis pathway of heme-iron has been well studied. Heme-iron is known to be synthesized by the following pathway: cyclic tetrapyrrole ring is formed from eight 5-aminolevulinic acid (5-ALA); side chains are transformed; and then reduced iron is combined thereto. Therefore, 5-ALA is a crucial substrate for heme-iron biosynthesis. The present inventors have studied to design a method for biologically producing heme-iron by increasing intracellular 5-ALA production, leading to the completion of this invention that overcomes the problems of using heme-iron products originated from animal blood.